Prospects of riboflavin carrier protein (RCP) as an antifertility vaccine in male and female mammals.
Riboflavin carrier protein (RCP) is obligatorily involved in yolk deposition of the vitamin, riboflavin, in the developing oocyte of the hen. The production of this protein is inducible by oestrogen. It is evolutionarily conserved in terms of its physicochemical, immunological and functional characteristics. It is the prime mediator of vitamin supply to the developing fetus in mammals, including primates. Passive immunoneutralization of the protein terminates pregnancy in rats. Active immunization of rats and bonnet monkeys with avian RCP prevents pregnancy without causing any adverse physiological effects of the mother in terms of her vitamin status, reproductive cycles or reproductive-endocrine profile. Denatured, linearized RCP is more effective in eliciting neutralizing antibodies capable of interfering with embryonic viability either before or during peri-implantation stages. Two defined stretches of sequential epitopes, one located at the N-terminus and the other at the C-terminus of the protein have been identified. Active immunization with either of these epitopes conjugated with diphtheria toxoid curtails pregnancy in rats and monkeys. Immunohistochemical localization of RCP on ovulated oocytes and early embryos shows that the antibodies cause degeneration only of early embryos. RCP is produced intra-testicularly and becomes localized on acrosomal surface of mammalian spermatozoa. Active immunization of male rats and monkeys with denatured RCP markedly reduces fertility by impairing the fertilizing potential of spermatozoa. These findings suggest that RCP, or its defined fragments, could be a novel, first generation vaccine for regulating fertility in both the sexes.
Adiga
P R
PR
Centre for Reproductive Biology and Molecular Endocrinology, Indian Institute of Science, Bangalore. adiga@serc.iisc.ernet.in
Subramanian
S
S
Rao
J
J
Kumar
M
M
D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000032:analysis / Q000737:chemistry / Q000276:immunology*; D002645:Chickens; D003269:Contraception, Immunologic / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D008322:Mammals; D026901:Membrane Transport Proteins; D008969:Molecular Sequence Data; D011247:Pregnancy; D012256:Riboflavin / Q000378:metabolism; D014612:Vaccines / Q000276:immunology
D002352:Carrier Proteins; D026901:Membrane Transport Proteins; D014612:Vaccines; C019079:riboflavin-binding protein; D012256:Riboflavin